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Jerry D Slater - One of the best experts on this subject based on the ideXlab platform.
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acute and late toxicity after dose escalation to 82 gye using conformal Proton Radiation for localized prostate cancer initial report of american college of radiology phase ii study 03 12
2011Co-Authors: John J Coen, Jerry D Slater, Kyounghwa Bae, Anthony L Zietman, Baldev Patel, William U Shipley, Carl J RossiAbstract:Purpose Several randomized trials have shown a benefit of dose escalation to 78 to 79 Gy for men treated with external Radiation for localized prostate cancer. Single-institution data suggest a benefit with even higher doses. American College of Radiology 03-12 is a Phase II trial testing the safety and efficacy of 82 GyE (Gray equivalent) delivered with conformal Proton Radiation. Methods and Materials From 2003–2006, 85 men with localized prostate cancer were accrued to American College of Radiology 03-12. Eighty-four were eligible for analysis. They were treated with conformal Proton Radiation alone to a total dose of 82 GyE. The study was designed to test whether the rate of 18-month Grade 3+ late toxicity was greater than 10%. Results The median follow-up was 31.6 months. Regarding treatment-related acute toxicity, there were 39 Grade 1 cases (46%), 19 Grade 2 cases (23%) and 2 Grade 3 cases (2%). Regarding genitourinary/gastrointestinal toxicity, there were 42 Grade 1 cases (50%), 12 Grade 2 cases (14%) and 1 Grade 3 case (1%). Regarding late toxicity, there were 28 Grade 1 cases (33%), 22 Grade 2 cases (26%), 6 Grade 3 cases (7%), and 1 Grade 4 case (1%). The late genitourinary/gastrointestinal rates were the same. The estimated rate of Grade 3+ late toxicity at 18 months was 6.08%. Conclusions Although not free of late toxicity, 82 GyE at 2 GyE per fraction delivered with conformal Proton Radiation did not exceed the late morbidity target tested in this trial. There was sufficient morbidity, however, that this may be the maximal dose that can be delivered safely with this technique and fractionation.
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patient reported long term outcomes after conventional and high dose combined Proton and photon Radiation for early prostate cancer
2010Co-Authors: James A Talcott, Jerry D Slater, Carl J Rossi, Andrzej Niemierko, William U Shipley, Jack A Clark, Anthony L ZietmanAbstract:Context Increased Radiation doses improve prostate cancer control but also increase toxicity to adjacent normal tissue. Proton Radiation may attenuate adverse effects. Objective To determine long-term, patient-reported, dose-related toxicity. Design, Setting, and Patients We performed a post hoc cross-sectional survey of surviving participants in the Proton Radiation Oncology Group (PROG) 9509—a randomized trial comparing 70.2 Gy vs 79.2 Gy of combined photon and Proton Radiation for 393 men with clinically localized prostate cancer (stage T1b-T2b, prostate-specific antigen Main Outcome Measures Prostate Cancer Symptom Indices, a validated measure of urinary incontinence, urinary obstruction and irritation, bowel problems, and sexual dysfunction, and related quality-of-life instruments. Results At a median of 9.4 years after treatment (range, 7.4-12.1 years), participants' demographic and clinical characteristics were similar. Patient-reported outcomes were reported as mean (SD) scale score for standard dose vs high dose: urinary obstruction/irritation (23.3 [13.7] vs 24.6 [14.0]; P = .36), urinary incontinence (10.6 [17.7] vs 9.7 [15.8]; P = .99), bowel problems (7.7 [7.8] vs 7.9 [9.1]; P = .70), sexual dysfunction (68.2 [34.6] vs 65.9 [34.7]; P = .65), and most other outcomes were also similar, although patients receiving standard dose whose cancers had more often progressed expressed less confidence that their cancers were under control (mean [SD] scale score for standard dose, 76.0 [25.4] vs high dose, 86.2 [17.9]; P Conclusion Among men with clinically localized prostate cancer, treatment with higher-dose Radiation compared with standard dose was not associated with an increase in patient-reported prostate cancer symptoms after a median of 9.4 years.
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development and operation of the loma linda university medical center Proton facility
2007Co-Authors: Jerry D SlaterAbstract:The Proton Treatment Center at Loma Linda University Medical Center, the world's first hospital-based Proton facility, opened in 1990 after two decades of development. Its early years were marked by a deliberately cautious approach in clinical utilization of Protons, with intent to establish hospital-based Proton therapy on a scientific basis. The facility was designed to be upgradeable, and development since 1990 has proceeded in three distinct phases of upgrades, both in technology and clinical applications. Upgrades continue, all of them based on an underlying program of basic and clinical research; future new applications of Proton Radiation therapy are expected to follow.
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clinical applications of Proton Radiation treatment at loma linda university review of a fifteen year experience
2006Co-Authors: Jerry D SlaterAbstract:Proton Radiation therapy has been used at Loma Linda University Medical Center for 15 years, sometimes in combination with photon irRadiation, surgery, and chemotherapy, but often as the sole modality. Our initial experience was based on established studies showing the utility of Protons for certain management problems, but since then we have engaged in a planned program to exploit the capabilities of Proton Radiation and expand its applications in accordance with progressively accumulating clinical data. Our cumulative experience has confirmed that Protons are a superb tool for delivering conformal Radiation treatments, enabling delivery of effective doses of Radiation and sparing normal tissues from Radiation exposure.
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Proton Radiation for treatment of cancer of the oropharynx early experience at loma linda university medical center using a concomitant boost technique
2005Co-Authors: Jerry D Slater, Roger Grove, Les T Yonemoto, David A Bush, William Preston, David W Mantik, Daniel W Miller, James M SlaterAbstract:Purpose: To assess accelerated fractionation using photon and Proton Radiation to improve local control and reduce complications in treating locally advanced oropharyngeal cancer. Methods and materials: Twenty-nine patients with localized Stage II–IV oropharyngeal cancer received accelerated photon and Proton Radiation, 75.9 GyE in 45 fractions/5.5 weeks, to the primary disease, involved lymph nodes, and potential areas of subclinical spread. Follow-up ranged from 2 to 96 months. Results: Five-year actuarial control for local disease was 88%, and for neck node disease, 96%; yielding a 84% locoregional control rate at 5 years. Four patients developed distant metastases. The 5-year actuarial locoregional control rate was 84%. The actuarial 2-year disease-free survival rate was 81%; at 5 years, it was 65%. All patients completed the prescribed treatment; though aggressive nutritional and anesthetic support was necessary. Late Grade 3 toxicity was seen in 3 patients. Conclusions: Protons used as a concomitant boost with photons effectively delivered an accelerated time–dose schedule to the cancer with a more tolerable schedule to surrounding normal tissues. Preliminary results reveal increased locoregional control without increased toxicity. Future studies must evaluate the optimum time–dose schedule.
Torunn I. Yock - One of the best experts on this subject based on the ideXlab platform.
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a comparison study assessing neuropsychological outcome of patients with post operative pediatric cerebellar mutism syndrome and matched controls after Proton Radiation therapy
2020Co-Authors: Julie A Grieco, Torunn I. Yock, Annah N Abrams, Casey L Evans, Margaret B PulsiferAbstract:Post-operative pediatric cerebellar mutism syndrome (CMS), characterized by mutism, ataxia/hypotonia, and emotional lability, can result in long-term deficits following resection of posterior fossa (PF) tumors. This longitudinal study compared neuropsychological outcomes of pediatric patients with post-operative CMS to a matched control patient group without CMS. Fifty-eight PF tumor patients received post-surgical Proton Radiation therapy (PRT) and testing at baseline and at ≥ 1-year post-PRT over a 10-year period. Of these, 18 (31%) had post-operative CMS with baseline and follow-up neuropsychological test data. Those participants were matched to 18 controls by tumor location, age, gender, and handedness; no significant group differences were found at baseline for clinical/demographic variables. Total mean age at baseline was 7.26 years (SD = 4.42); mean follow-up interval was 3.26 years (SD = 2.24). Areas assessed: overall intelligence, expressive and receptive vocabulary, visuomotor integration, fine motor speed, inhibition, emotional control, depression, and anxiety. Patients were 52% male; 86% medulloblastoma/14% ependymoma; 86% craniospinal irRadiation/14% focal Radiation; and 86% chemotherapy. No group differences were found between most mean baseline scores; expressive vocabulary and fine motor speed were significantly lower in the post-operative CMS group (p < 0.05). Mean change scores revealed no significant differences for the sample; scores were within the normal range except fine motor skills were impaired for both groups. Longitudinal neuropsychological outcomes for post-operative pediatric CMS patients did not differ significantly from matched controls without this condition. Patients were in the normal range in all areas except fine motor speed, which was impaired for both groups independent of CMS diagnosis.
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cognitive and adaptive outcomes after Proton Radiation for pediatric patients with brain tumors
2018Co-Authors: Margaret B Pulsifer, Shannon M Macdonald, Nancy J Tarbell, Julie A Grieco, Casey L Evans, Haley Duncanson, Irene Delgado Tseretopoulos, Torunn I. YockAbstract:Purpose Radiation therapy is integral in treatment of pediatric brain tumors, but it is associated with negative long-term sequelae. Proton beam Radiation therapy (PRT), which enables better focusing of Radiation on tumors, may entail fewer sequelae. This prospective study examined cognitive and adaptive functioning in children and young adults treated with PRT. Methods and Materials A total of 155 patients were assessed using age-appropriate measures for cognitive and adaptive functioning at start of or during PRT (baseline) and at follow-up. Mean age at baseline was 8.9 years; mean follow-up interval was 3.6 years. Diagnoses included medulloblastoma, craniopharyngioma, ependymoma, glial tumors, germ cell tumors, and others. The sample was divided by age at baseline ( Results Scores for mean intelligence quotient (IQ) and adaptive functioning skills were in the average range at baseline and follow-up. Overall, mean IQ scores declined from 105.4 to 102.5 ( P = .005); however, only the younger CSI group showed significant decline. Patients receiving CSI, regardless of age, appeared particularly vulnerable in IQ, processing speed, and working memory. Adaptive skills were stable across the 4 age-by-treatment field groups. Conclusions At a mean of 3.6 years after PRT, IQ declined slightly for the group, largely because of significant IQ decline in younger patients treated with CSI. No significant change was seen in patients
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cognitive and adaptive outcomes after Proton Radiation for pediatric patients with brain tumors
2018Co-Authors: Margaret B Pulsifer, Shannon M Macdonald, Nancy J Tarbell, Julie A Grieco, Casey L Evans, Haley Duncanson, Irene Delgado Tseretopoulos, Torunn I. YockAbstract:PURPOSE Radiation therapy is integral in treatment of pediatric brain tumors, but it is associated with negative long-term sequelae. Proton beam Radiation therapy (PRT), which enables better focusing of Radiation on tumors, may entail fewer sequelae. This prospective study examined cognitive and adaptive functioning in children and young adults treated with PRT. METHODS AND MATERIALS A total of 155 patients were assessed using age-appropriate measures for cognitive and adaptive functioning at start of or during PRT (baseline) and at follow-up. Mean age at baseline was 8.9 years; mean follow-up interval was 3.6 years. Diagnoses included medulloblastoma, craniopharyngioma, ependymoma, glial tumors, germ cell tumors, and others. The sample was divided by age at baseline (<6 years [N = 57, or 37%] and ≥6 years [N = 98, or 63%]) and by PRT field (craniospinal irRadiation [CSI; 39%] and focal irRadiation [61%]). RESULTS Scores for mean intelligence quotient (IQ) and adaptive functioning skills were in the average range at baseline and follow-up. Overall, mean IQ scores declined from 105.4 to 102.5 (P = .005); however, only the younger CSI group showed significant decline. Patients receiving CSI, regardless of age, appeared particularly vulnerable in IQ, processing speed, and working memory. Adaptive skills were stable across the 4 age-by-treatment field groups. CONCLUSIONS At a mean of 3.6 years after PRT, IQ declined slightly for the group, largely because of significant IQ decline in younger patients treated with CSI. No significant change was seen in patients <6 years treated with focal PRT or in older patients. Adaptive skills remained stable across age and treatment type.
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analysis of patient outcomes following Proton Radiation therapy for retinoblastoma
2017Co-Authors: Kent W Mouw, Beow Y Yeap, Roshan V Sethi, Shannon M Macdonald, Nancy J Tarbell, Yenlin Chen, Paul A Caruso, Aaron Fay, Madhusmita Misra, Torunn I. YockAbstract:Abstract Purpose Proton Radiation therapy (PRT) is used to treat patients with retinoblastoma (RB) and has the potential to minimize exposure of normal tissue to Radiation and thus decrease the risk of toxicity and second malignancies. However, comprehensive analyses of long-term patient outcomes are not available. Methods and materials Patients with RB who were treated with PRT at our institution between 1986 and 2012 were invited to participate in a study that was designed to assess long-term outcomes. Patients who were enrolled in the study underwent a comprehensive analysis that included oncologic, ophthalmic, endocrine, cephalometric, and quality of life (QOL) assessments. Results A total of 12 patients were enrolled in this study. The average length of follow-up was 12.9 years (range, 4.8-22.2 years). All study patients had bilateral disease, and the disease and visual outcomes were similar to the outcomes for all patients with RB who were treated with PRT over the same time period at our institution. An analysis of endocrine-related test results revealed no growth abnormalities or hormonal deficiencies across the cohort. Magnetic resonance imaging scans and external cephalometry showed that PRT was associated with less facial hypoplasia than enucleation. Patient and parent-proxy QOL assessments revealed that treatment for RB did not appear to severely affect long-term QOL. Conclusions In addition to providing an opportunity for long-term disease control and functional eye preservation, PRT does not appear to be associated with unexpected late visual, endocrine, or QOL effects in this cohort of patients with RB.
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Successful Treatment of Recurrent Li-Fraumeni Syndrome-related Choroid Plexus Carcinoma.
2017Co-Authors: Matthew Mcevoy, Nathan Robison, Peter E. Manley, Torunn I. Yock, Kristine E. Konopka, Robert E. Brown, Johannes E. Wolff, Adam L. GreenAbstract:The management of choroid plexus carcinoma (CPC) is challenging and multifaceted. Here, we discuss a 3-year-old girl with CPC and Li-Fraumeni syndrome who achieved full remission after surgery and chemotherapy, with Radiation therapy spared. At recurrence, we used a novel, standard-dose cytotoxic chemotherapy regimen, focal Proton Radiation therapy, and targeted agents based on morphoproteomic analysis to achieve long-term survival. We highlight the rationale for our therapy at recurrence, as well as the risk-benefit analyses necessary in decision making for these patients. Our strategy may be effective in managing other patients with recurrent CPC and Li-Fraumeni syndrome.
Nancy J Tarbell - One of the best experts on this subject based on the ideXlab platform.
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cognitive and adaptive outcomes after Proton Radiation for pediatric patients with brain tumors
2018Co-Authors: Margaret B Pulsifer, Shannon M Macdonald, Nancy J Tarbell, Julie A Grieco, Casey L Evans, Haley Duncanson, Irene Delgado Tseretopoulos, Torunn I. YockAbstract:Purpose Radiation therapy is integral in treatment of pediatric brain tumors, but it is associated with negative long-term sequelae. Proton beam Radiation therapy (PRT), which enables better focusing of Radiation on tumors, may entail fewer sequelae. This prospective study examined cognitive and adaptive functioning in children and young adults treated with PRT. Methods and Materials A total of 155 patients were assessed using age-appropriate measures for cognitive and adaptive functioning at start of or during PRT (baseline) and at follow-up. Mean age at baseline was 8.9 years; mean follow-up interval was 3.6 years. Diagnoses included medulloblastoma, craniopharyngioma, ependymoma, glial tumors, germ cell tumors, and others. The sample was divided by age at baseline ( Results Scores for mean intelligence quotient (IQ) and adaptive functioning skills were in the average range at baseline and follow-up. Overall, mean IQ scores declined from 105.4 to 102.5 ( P = .005); however, only the younger CSI group showed significant decline. Patients receiving CSI, regardless of age, appeared particularly vulnerable in IQ, processing speed, and working memory. Adaptive skills were stable across the 4 age-by-treatment field groups. Conclusions At a mean of 3.6 years after PRT, IQ declined slightly for the group, largely because of significant IQ decline in younger patients treated with CSI. No significant change was seen in patients
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cognitive and adaptive outcomes after Proton Radiation for pediatric patients with brain tumors
2018Co-Authors: Margaret B Pulsifer, Shannon M Macdonald, Nancy J Tarbell, Julie A Grieco, Casey L Evans, Haley Duncanson, Irene Delgado Tseretopoulos, Torunn I. YockAbstract:PURPOSE Radiation therapy is integral in treatment of pediatric brain tumors, but it is associated with negative long-term sequelae. Proton beam Radiation therapy (PRT), which enables better focusing of Radiation on tumors, may entail fewer sequelae. This prospective study examined cognitive and adaptive functioning in children and young adults treated with PRT. METHODS AND MATERIALS A total of 155 patients were assessed using age-appropriate measures for cognitive and adaptive functioning at start of or during PRT (baseline) and at follow-up. Mean age at baseline was 8.9 years; mean follow-up interval was 3.6 years. Diagnoses included medulloblastoma, craniopharyngioma, ependymoma, glial tumors, germ cell tumors, and others. The sample was divided by age at baseline (<6 years [N = 57, or 37%] and ≥6 years [N = 98, or 63%]) and by PRT field (craniospinal irRadiation [CSI; 39%] and focal irRadiation [61%]). RESULTS Scores for mean intelligence quotient (IQ) and adaptive functioning skills were in the average range at baseline and follow-up. Overall, mean IQ scores declined from 105.4 to 102.5 (P = .005); however, only the younger CSI group showed significant decline. Patients receiving CSI, regardless of age, appeared particularly vulnerable in IQ, processing speed, and working memory. Adaptive skills were stable across the 4 age-by-treatment field groups. CONCLUSIONS At a mean of 3.6 years after PRT, IQ declined slightly for the group, largely because of significant IQ decline in younger patients treated with CSI. No significant change was seen in patients <6 years treated with focal PRT or in older patients. Adaptive skills remained stable across age and treatment type.
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analysis of patient outcomes following Proton Radiation therapy for retinoblastoma
2017Co-Authors: Kent W Mouw, Beow Y Yeap, Roshan V Sethi, Shannon M Macdonald, Nancy J Tarbell, Yenlin Chen, Paul A Caruso, Aaron Fay, Madhusmita Misra, Torunn I. YockAbstract:Abstract Purpose Proton Radiation therapy (PRT) is used to treat patients with retinoblastoma (RB) and has the potential to minimize exposure of normal tissue to Radiation and thus decrease the risk of toxicity and second malignancies. However, comprehensive analyses of long-term patient outcomes are not available. Methods and materials Patients with RB who were treated with PRT at our institution between 1986 and 2012 were invited to participate in a study that was designed to assess long-term outcomes. Patients who were enrolled in the study underwent a comprehensive analysis that included oncologic, ophthalmic, endocrine, cephalometric, and quality of life (QOL) assessments. Results A total of 12 patients were enrolled in this study. The average length of follow-up was 12.9 years (range, 4.8-22.2 years). All study patients had bilateral disease, and the disease and visual outcomes were similar to the outcomes for all patients with RB who were treated with PRT over the same time period at our institution. An analysis of endocrine-related test results revealed no growth abnormalities or hormonal deficiencies across the cohort. Magnetic resonance imaging scans and external cephalometry showed that PRT was associated with less facial hypoplasia than enucleation. Patient and parent-proxy QOL assessments revealed that treatment for RB did not appear to severely affect long-term QOL. Conclusions In addition to providing an opportunity for long-term disease control and functional eye preservation, PRT does not appear to be associated with unexpected late visual, endocrine, or QOL effects in this cohort of patients with RB.
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secondary malignancy risk following Proton Radiation therapy
2015Co-Authors: Bree R Eaton, Torunn I. Yock, Shannon M Macdonald, Nancy J TarbellAbstract:Radiation-induced secondary malignancies are a significant, yet uncommon cause of morbidity and mortality among cancer survivors. Secondary malignancy risk is dependent upon multiple factors including patient age, the biological and genetic predisposition of the individual, the volume and location of tissue irradiated, and the dose of Radiation received. Proton therapy (PRT) is an advanced particle therapy with unique dosimetric properties resulting in reduced entrance dose and minimal to no exit dose when compared with standard photon Radiation therapy. Multiple dosimetric studies in varying cancer subtypes have demonstrated that PRT enables the delivery of adequate target volume coverage with reduced integral dose delivered to surrounding tissues, and modeling studies taking into account dosimetry and Radiation cell biology have estimated a significantly reduced risk of Radiation-induced secondary malignancy with PRT. Clinical data are emerging supporting the lower incidence of secondary malignancies after PRT compared with historical photon data, though longer follow-up in Proton treated cohorts is awaited. This article reviews the current dosimetric and clinical literature evaluating the incidence of and risk factors associated with Radiation-induced secondary malignancy following PRT.
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early cognitive outcomes following Proton Radiation in pediatric patients with brain and central nervous system tumors
2015Co-Authors: Margaret B Pulsifer, Roshan V Sethi, Karen Kuhlthau, Shannon M Macdonald, Nancy J Tarbell, Torunn I. YockAbstract:Purpose To report, from a longitudinal study, cognitive outcome in pediatric patients treated with Proton Radiation therapy (PRT) for central nervous system (CNS) tumors. Methods and Materials Sixty patients receiving PRT for medulloblastoma (38.3%), gliomas (18.3%), craniopharyngioma (15.0%), ependymoma (11.7%), and other CNS tumors (16.7%) were administered age-appropriate measures of cognitive abilities at or near PRT initiation (baseline) and afterward (follow-up). Patients were aged ≥6 years at baseline to ensure consistency in neurocognitive measures. Results Mean age was 12.3 years at baseline; mean follow-up interval was 2.5 years. Treatment included prior surgical resection (76.7%) and chemotherapy (61.7%). Proton Radiation therapy included craniospinal irRadiation (46.7%) and partial brain Radiation (53.3%). At baseline, mean Wechsler Full Scale IQ was 104.6; means of all 4 Index scores were also in the average range. At follow-up, no significant change was observed in mean Wechsler Full Scale IQ, Verbal Comprehension, Perceptual Reasoning/Organization, or Working Memory. However, Processing Speed scores declined significantly (mean 5.2 points), with a significantly greater decline for subjects aged Conclusions Early cognitive outcomes after PRT for pediatric CNS tumors are encouraging, compared with published outcomes from photon Radiation therapy.
James M Slater - One of the best experts on this subject based on the ideXlab platform.
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Proton Radiation for treatment of cancer of the oropharynx early experience at loma linda university medical center using a concomitant boost technique
2005Co-Authors: Jerry D Slater, Roger Grove, Les T Yonemoto, David A Bush, William Preston, David W Mantik, Daniel W Miller, James M SlaterAbstract:Purpose: To assess accelerated fractionation using photon and Proton Radiation to improve local control and reduce complications in treating locally advanced oropharyngeal cancer. Methods and materials: Twenty-nine patients with localized Stage II–IV oropharyngeal cancer received accelerated photon and Proton Radiation, 75.9 GyE in 45 fractions/5.5 weeks, to the primary disease, involved lymph nodes, and potential areas of subclinical spread. Follow-up ranged from 2 to 96 months. Results: Five-year actuarial control for local disease was 88%, and for neck node disease, 96%; yielding a 84% locoregional control rate at 5 years. Four patients developed distant metastases. The 5-year actuarial locoregional control rate was 84%. The actuarial 2-year disease-free survival rate was 81%; at 5 years, it was 65%. All patients completed the prescribed treatment; though aggressive nutritional and anesthetic support was necessary. Late Grade 3 toxicity was seen in 3 patients. Conclusions: Protons used as a concomitant boost with photons effectively delivered an accelerated time–dose schedule to the cancer with a more tolerable schedule to surrounding normal tissues. Preliminary results reveal increased locoregional control without increased toxicity. Future studies must evaluate the optimum time–dose schedule.
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Proton therapy for prostate cancer the initial loma linda university experience
2004Co-Authors: Jerry D Slater, Roger Grove, Carl J Rossi, Les T Yonemoto, David A Bush, Rodney B Jabola, Richard P Levy, William Preston, James M SlaterAbstract:Abstract Purpose We analyzed results of conformal Proton Radiation therapy for localized prostate cancer, with emphasis on biochemical freedom from relapse. Methods and materials Analyses were performed for 1255 patients treated between October 1991 and December 1997. Outcomes were measured on primarily in terms of biochemical relapse and toxicity. Results The overall biochemical disease-free survival rate was 73%, and was 90% in patients with initial PSA ≤4.0; it was 87% in patients with posttreatment PSA nadirs ≤0.50. Rates dropped with rises in initial and nadir PSA values. Long-term survival outcomes were comparable with those reported for other modalities intended for cure. Conclusions Conformal Proton Radiation therapy at the reported dose levels yielded disease-free survival rates comparable with other forms of local therapy, and with minimal morbidity. Dose-escalation strategies are being implemented to further improve long-term results.
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Proton Radiation therapy prt for pediatric optic pathway gliomas comparison with 3d planned conventional photons and a standard photon technique
1999Co-Authors: Martin Fuss, Eugen B Hug, Rosemary A Schaefer, James M Slater, Daniel W Miller, Meinhard Nevinnystickel, Jerry D SlaterAbstract:Abstract Purpose: Following adequate therapy, excellent long-term survival rates can be achieved for patients with optic pathway gliomas. Therefore, avoidance of treatment-related functional long-term sequelae is of utmost importance. Optimized sparing of normal tissue is of primary concern in the development of new treatment modalities. The present study compares Proton Radiation therapy (PRT) with a three-dimensional (3D)-planned multiport photon and a lateral beam photon technique for localized and extensive optic pathway tumors. Methods and Materials: Between February 1992 and November 1997, seven children with optic pathway gliomas underwent PRT. For this study, we computed Proton, 3D photon, and lateral photon plans based on the same CT data sets, and using the same treatment planning software for all plans. Radiation exposure for normal tissue and discrete organs at risk was quantified based on dose-volume histograms. Results: Gross tumor volume (GTV) ranged from 3.9 cm 3 to 127.2 cm 3 . Conformity index (relation of encompassing isodose to GTV volume) was 2.3 for Protons, 2.9 for 3D photons, and 7.3 for lateral photons. The relative increase of normal tissue (NT) encompassed at several isodose levels in relation to NT encompassed by the 95% Proton isodose volume was computed. Relative NT volume of Proton plan isodoses at the 95%, 90%, 80%, 50%, and 25% isodose level increased from 1 to 1.6, 2.8, 6.4, to a maximum of 13.3. Relative volumes for 3D photons were 1.6, 2.4, 3.8, 11.5, and 34.8. Lateral plan relative values were 6, 8.3, 11.5, 19.2, and 26.8. Analysis for small ( 3 ) and larger (> 80 cm 3 ) tumors showed that Protons encompassed the smallest volumes of NT at all isodose levels. Comparable conformity and high-dose gradient were achieved for Proton and 3D photon plans in small tumors. However, with increasing tumor volume and complexity, differences became larger. At the 50% isodose level, 3D photons were superior to lateral photons for small tumors; this advantage was equalized for larger tumors. At the lowest isodose level, 3D photons encompassed the highest amount of NT. Analysis of organs at risk showed that PRT reduced doses to the contralateral optic nerve by 47% and 77% compared to 3D photons and lateral photons, respectively. Reductions were also seen for the chiasm (11% and 16%) and pituitary gland (13% and 16%), with differences at clinically relevant tolerance levels. Furthermore, reduced dose exposure of both temporal lobes (sparing 39% and 54%) and frontal lobes was achieved with PRT. Conclusion: PRT offered a high degree of conformity to target volumes and steep dose gradients, thus leading to substantial normal tissue sparing in high- and low-dose areas. It is expected that this will result in decreased long-term toxicity in the maturing child. Advantages of Proton versus 3D photon plans became increasingly apparent with increasing target size and tumor complexity. Even in small tumors, conformity of 3D photon irRadiation came at the expense of a larger amount of NT receiving moderate to low Radiation doses. Lateral photons resulted in inferior dose distribution with high Radiation exposure of clinically relevant normal tissues.
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Proton Radiation therapy for chordomas and chondrosarcomas of the skull base
1999Co-Authors: Eugen B Hug, Lilia N Loredo, Jerry D Slater, A Devries, Roger Grove, Rosemary A Schaefer, Andrew E Rosenberg, James M SlaterAbstract:Object. Local tumor control, patient survival, and treatment failure outcomes were analyzed to assess treatment efficacy in 58 patients in whom fractionated Proton Radiation therapy (RT) was administered for skull base chordomas and chondrosarcomas. Methods. Between March 1992 and January 1998, a total of 58 patients who could be evaluated were treated for skull base tumors, 33 for chordoma and 25 for chondrosarcoma. Following various surgical procedures, residual tumor was detected in 91% of patients; 59% demonstrated brainstem involvement. Target dosages ranged from 64.8 and 79.2 (mean 70.7) Co Gy equivalent. The range of follow up was 7 to 75 months (mean 33 months). In 10 patients (17%) the treatment failed locally, resulting in local control rates of 92% (23 of 25 patients) for chondrosarcomas and 76% (25 of 33 patients) for chordomas. Tumor volume and brainstem involvement influenced control rates. All tumors with volumes of 25 ml or less remained locally controlled, compared with 56% of tumors larg...
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Proton Radiation therapy for chordomas and chondrosarcomas of the skull base
1999Co-Authors: Eugen B Hug, Lilia N Loredo, Jerry D Slater, A Devries, Roger Grove, Rosemary A Schaefer, Andrew E Rosenberg, James M SlaterAbstract:Object Local tumor control, patient survival, and treatment failure outcomes were analyzed to assess treatment efficacy in 58 patients in whom fractionated Proton Radiation therapy (RT) was administered for skull base chordomas and chondrosarcomas. Methods Between March 1992 and January 1998, a total of 58 patients who could be evaluated were treated for skull base tumors, 33 for chordoma and 25 for chondrosarcoma. Following various surgical procedures, residual tumor was detected in 91% of patients; 59% demonstrated brainstem involvement. Target dosages ranged from 64.8 and 79.2 (mean 70.7) Co Gy equivalent. The range of follow up was 7 to 75 months (mean 33 months). In 10 patients (17%) the treatment failed locally, resulting in local control rates of 92% (23 of 25 patients) for chondrosarcomas and 76% (25 of 33 patients) for chordomas. Tumor volume and brainstem involvement influenced control rates. All tumors with volumes of 25 ml or less remained locally controlled, compared with 56% of tumors larger than 25 ml (p = 0.02); 94% of patients without brainstem involvement did not experience recurrence; in patients with brainstem involvement (and dose reduction because of brainstem tolerance constraints) the authors achieved a tumor control rate of 53% (p = 0.04). Three patients died of their disease, and one died of intercurrent disease. Actuarial 5-year survival rates were 100% for patients with chondrosarcoma and 79% for patients with chordoma. Grade 3 and 4 late toxicities were observed in four patients (7%) and were symptomatic in three (5%). Conclusions High-dose Proton RT offers excellent chances of lasting tumor control and survival, with acceptable risks. In this series all small- and medium-sized tumors with no demonstrable brainstem involvement have been controlled; all such patients are alive. Surgical debulking enhanced delivery of full tumoricidal doses, but even patients with large tumors and disease abutting crucial normal structures benefited.
Shannon M Macdonald - One of the best experts on this subject based on the ideXlab platform.
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cognitive and adaptive outcomes after Proton Radiation for pediatric patients with brain tumors
2018Co-Authors: Margaret B Pulsifer, Shannon M Macdonald, Nancy J Tarbell, Julie A Grieco, Casey L Evans, Haley Duncanson, Irene Delgado Tseretopoulos, Torunn I. YockAbstract:PURPOSE Radiation therapy is integral in treatment of pediatric brain tumors, but it is associated with negative long-term sequelae. Proton beam Radiation therapy (PRT), which enables better focusing of Radiation on tumors, may entail fewer sequelae. This prospective study examined cognitive and adaptive functioning in children and young adults treated with PRT. METHODS AND MATERIALS A total of 155 patients were assessed using age-appropriate measures for cognitive and adaptive functioning at start of or during PRT (baseline) and at follow-up. Mean age at baseline was 8.9 years; mean follow-up interval was 3.6 years. Diagnoses included medulloblastoma, craniopharyngioma, ependymoma, glial tumors, germ cell tumors, and others. The sample was divided by age at baseline (<6 years [N = 57, or 37%] and ≥6 years [N = 98, or 63%]) and by PRT field (craniospinal irRadiation [CSI; 39%] and focal irRadiation [61%]). RESULTS Scores for mean intelligence quotient (IQ) and adaptive functioning skills were in the average range at baseline and follow-up. Overall, mean IQ scores declined from 105.4 to 102.5 (P = .005); however, only the younger CSI group showed significant decline. Patients receiving CSI, regardless of age, appeared particularly vulnerable in IQ, processing speed, and working memory. Adaptive skills were stable across the 4 age-by-treatment field groups. CONCLUSIONS At a mean of 3.6 years after PRT, IQ declined slightly for the group, largely because of significant IQ decline in younger patients treated with CSI. No significant change was seen in patients <6 years treated with focal PRT or in older patients. Adaptive skills remained stable across age and treatment type.
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cognitive and adaptive outcomes after Proton Radiation for pediatric patients with brain tumors
2018Co-Authors: Margaret B Pulsifer, Shannon M Macdonald, Nancy J Tarbell, Julie A Grieco, Casey L Evans, Haley Duncanson, Irene Delgado Tseretopoulos, Torunn I. YockAbstract:Purpose Radiation therapy is integral in treatment of pediatric brain tumors, but it is associated with negative long-term sequelae. Proton beam Radiation therapy (PRT), which enables better focusing of Radiation on tumors, may entail fewer sequelae. This prospective study examined cognitive and adaptive functioning in children and young adults treated with PRT. Methods and Materials A total of 155 patients were assessed using age-appropriate measures for cognitive and adaptive functioning at start of or during PRT (baseline) and at follow-up. Mean age at baseline was 8.9 years; mean follow-up interval was 3.6 years. Diagnoses included medulloblastoma, craniopharyngioma, ependymoma, glial tumors, germ cell tumors, and others. The sample was divided by age at baseline ( Results Scores for mean intelligence quotient (IQ) and adaptive functioning skills were in the average range at baseline and follow-up. Overall, mean IQ scores declined from 105.4 to 102.5 ( P = .005); however, only the younger CSI group showed significant decline. Patients receiving CSI, regardless of age, appeared particularly vulnerable in IQ, processing speed, and working memory. Adaptive skills were stable across the 4 age-by-treatment field groups. Conclusions At a mean of 3.6 years after PRT, IQ declined slightly for the group, largely because of significant IQ decline in younger patients treated with CSI. No significant change was seen in patients
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analysis of patient outcomes following Proton Radiation therapy for retinoblastoma
2017Co-Authors: Kent W Mouw, Beow Y Yeap, Roshan V Sethi, Shannon M Macdonald, Nancy J Tarbell, Yenlin Chen, Paul A Caruso, Aaron Fay, Madhusmita Misra, Torunn I. YockAbstract:Abstract Purpose Proton Radiation therapy (PRT) is used to treat patients with retinoblastoma (RB) and has the potential to minimize exposure of normal tissue to Radiation and thus decrease the risk of toxicity and second malignancies. However, comprehensive analyses of long-term patient outcomes are not available. Methods and materials Patients with RB who were treated with PRT at our institution between 1986 and 2012 were invited to participate in a study that was designed to assess long-term outcomes. Patients who were enrolled in the study underwent a comprehensive analysis that included oncologic, ophthalmic, endocrine, cephalometric, and quality of life (QOL) assessments. Results A total of 12 patients were enrolled in this study. The average length of follow-up was 12.9 years (range, 4.8-22.2 years). All study patients had bilateral disease, and the disease and visual outcomes were similar to the outcomes for all patients with RB who were treated with PRT over the same time period at our institution. An analysis of endocrine-related test results revealed no growth abnormalities or hormonal deficiencies across the cohort. Magnetic resonance imaging scans and external cephalometry showed that PRT was associated with less facial hypoplasia than enucleation. Patient and parent-proxy QOL assessments revealed that treatment for RB did not appear to severely affect long-term QOL. Conclusions In addition to providing an opportunity for long-term disease control and functional eye preservation, PRT does not appear to be associated with unexpected late visual, endocrine, or QOL effects in this cohort of patients with RB.
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secondary malignancy risk following Proton Radiation therapy
2015Co-Authors: Bree R Eaton, Torunn I. Yock, Shannon M Macdonald, Nancy J TarbellAbstract:Radiation-induced secondary malignancies are a significant, yet uncommon cause of morbidity and mortality among cancer survivors. Secondary malignancy risk is dependent upon multiple factors including patient age, the biological and genetic predisposition of the individual, the volume and location of tissue irradiated, and the dose of Radiation received. Proton therapy (PRT) is an advanced particle therapy with unique dosimetric properties resulting in reduced entrance dose and minimal to no exit dose when compared with standard photon Radiation therapy. Multiple dosimetric studies in varying cancer subtypes have demonstrated that PRT enables the delivery of adequate target volume coverage with reduced integral dose delivered to surrounding tissues, and modeling studies taking into account dosimetry and Radiation cell biology have estimated a significantly reduced risk of Radiation-induced secondary malignancy with PRT. Clinical data are emerging supporting the lower incidence of secondary malignancies after PRT compared with historical photon data, though longer follow-up in Proton treated cohorts is awaited. This article reviews the current dosimetric and clinical literature evaluating the incidence of and risk factors associated with Radiation-induced secondary malignancy following PRT.
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early cognitive outcomes following Proton Radiation in pediatric patients with brain and central nervous system tumors
2015Co-Authors: Margaret B Pulsifer, Roshan V Sethi, Karen Kuhlthau, Shannon M Macdonald, Nancy J Tarbell, Torunn I. YockAbstract:Purpose To report, from a longitudinal study, cognitive outcome in pediatric patients treated with Proton Radiation therapy (PRT) for central nervous system (CNS) tumors. Methods and Materials Sixty patients receiving PRT for medulloblastoma (38.3%), gliomas (18.3%), craniopharyngioma (15.0%), ependymoma (11.7%), and other CNS tumors (16.7%) were administered age-appropriate measures of cognitive abilities at or near PRT initiation (baseline) and afterward (follow-up). Patients were aged ≥6 years at baseline to ensure consistency in neurocognitive measures. Results Mean age was 12.3 years at baseline; mean follow-up interval was 2.5 years. Treatment included prior surgical resection (76.7%) and chemotherapy (61.7%). Proton Radiation therapy included craniospinal irRadiation (46.7%) and partial brain Radiation (53.3%). At baseline, mean Wechsler Full Scale IQ was 104.6; means of all 4 Index scores were also in the average range. At follow-up, no significant change was observed in mean Wechsler Full Scale IQ, Verbal Comprehension, Perceptual Reasoning/Organization, or Working Memory. However, Processing Speed scores declined significantly (mean 5.2 points), with a significantly greater decline for subjects aged Conclusions Early cognitive outcomes after PRT for pediatric CNS tumors are encouraging, compared with published outcomes from photon Radiation therapy.
